3-Deoxy-1{60 -hydroxycholecalciferol

ABSTRACT

3-deoxy-1 Alpha -hydroxycholecalciferol. The compound is characterized by vitamin D-like activity.

United States Patent DeLuca et al.

3-DEOXY-l a- HYDROXYCl-IOLECALCIFEROL inventors: Hector F. DeLuca, Madison;

Heinrich K. Schnoes, Waunakee; Hing-Yat Lam, Madison. all of Wis.

Assignee: Wisconsin Alumni Research Foundation, Madison, Wis.

Filed: June 17, 1974 Appl. No.: 480,2"

U.S. Cl. 260/3973 Int. Cl. C07J 9/00 Field of Search 260/3971 [4 1 Sept. 16, 1975 Primary ExaminerEibert L. Roberts Attorney. Agent. or Firm-Howard W. Bremer ABSTRACT 3-deoxy-la-hydroxychoiecalciferol. The compound is characterized by vitamin D-iike activity.

3 Claims, No Drawings 3-DEOXY-l a-HYDROXYCHOLECALCIFEROL The invention described herein was made in the course of work under a grant or award from the De partment of Health, Education, and Welfare.

This invention related to a compound which exhibits vitamin D-likc activity.

More particularly, this invention relates to a derivative of vitamin D The D vitamins, particularly vitamins D and D have long been known and applied for their effect upon deficiency type diseases involving calcium metabolism such as, for example, rickets. In more recent years vari ous derivatives of the D vitamins have been discovered which exhibit an antirachitic effect greater than that exhibited by vitamin D or D;,. Other derivatives of vitamin D and D have been discovered which show more specific activity in calcium metabolic activity such as enhancing calcium transport in the gut or increasing or decreasing bone calcium mobilization.

A new derivative of vitamin D, has now been synthesized which exhibits vitamin D-like activity in promoting intestinal calcium transport and in increasing bone calcium mobilization. This vitamin D derivative has been identified as 3-deoxy-la-hydroxycholeealciferol.

SYNTHESIS In the following description identification of the various intermediate compounds and of the 3-deoxy compound claimed was established utilizing the following instrumentation, carriers and analytical reagents and aids.

Also, like numbers identify identical compounds in the description and in the process schematics which follow.

For column chromatography silicic acid (Mallinckrodt Chemical Co., 100 mesh), neutral alumina (Bio- Rad minus 200 mesh, California Corp. for Biochemical Research, Los Angeles, Calif.) or Sephadex LH-20 (a hydroxypropyl ether derivative of a polydextran marketed by Pharmacia Fine Chemicals, Inc., Piscataway, NJ.) was used. Thin layer plates were coated with Merck silica gel G and air dried. Sulfuric acid spray or iodine vapor was used for visualization of spots. Skellysolve B (essentially normal hexane, derived from petroleum oil, marketed by Skelley Oil Co.) for reactions and chromatography was redistilled and the fraction boiling at 6769 was used. Melting points were determined on a hot stage and are uncorrected. Infrared spectra (ir) were recorded on a Beckman Instruments, Inc. model IR-5 instrument; ultraviolet spectra (uv) were obtained with a Beckman Instruments, Inc. model DBG spectrophotometer. Mass spectra were determined with an Associated Electrical Industries model MS-902 double focussing mass spectrometer. Electron impact ionization at 70 cV was used. Perfluorotributylamine was used as standard for accurate mass measurements. Nuclear magnetic resonance (nmr) spectra were measured on a Varian Associates model T 60 instrument and data are given in p.p.m. (8) downfield from tetramethylsilane as internal standard. Gas liquid chromatography (glc) was performed on an F & M model 402 instrument (Hewlett-Packard Co., Avondale, Pa. using 4 ft. X A in. glass columns packed with 3% SE30 on l00l mesh Gas Chrom Z (a silicone oil on a ceramic carrier available from Hewlett Packard Co.) utilizing a column temperature of 250 C and an outflow rate of 80 ml/min. Mieroanalyses were performed by MicrowTech Laboratories, Inc., Skokie, Illinois.

A stirred solution of cholesterol (1,60 g) in 240 ml glacial acetic acid was treated dropwise with 4.5 ml

- fuming nitric acid. The mixture was then cooled in an ice-salt bath and additional fuming nitric acid (390 ml) was added over a 1 hr period and stirring was continued for another 0.5 hr. The reaction mixture was then rapidly filtered by suction, the filter cake was taken up in 570 ml glacial acetic acid and after additional of 107 m1 H 0 and Zn dust (7] g) heated for 1 hr on a steam bath. After refluxing for an additional 10 hr period the reaction mixture was diluted with H 0 and extracted with diethyl ether. The ether layer was separated and evaporated to dryness. To the residue, 400 ml of I00% ethanol and ml concentrated HCI were added and the solution refluxed for 2 hr. Enough H O was then added to induce slight turbidity, and the product allowed to crystallize. Recrystallization from aqueous ethanol yielded 25 g (yield 40%) of pure 3B-hydroxy- 5a-cholestan-6-one(2): m.p l42.5l44; mass spectrum: m/e 402 M", 100% and m/e 387 (8%), 384 (7%), 369 (7%), 331 (6%), 289 (17%), 262 (9%), 247 (17%), 248 (17%); ir (CHCI 1712 (C=O), 3400 (OH) cm"; Anal. calcd, for C H O C, 80.54; H, 1141; found: c, 80.52; H, ll.62.

15 grams of 3B-hydroxy-5a-cholestan-6-one was dissolved in redistilled (6769) Skellysolve B. To this solution freshly distilled ethylene glycol (50 ml) and p-toluenesulfonic acid monohydrate (IOO'mg) were added in a one-liter round bottom flask fitted with a Dean-Stark trap, and the mixture was refluxed for 22 hr with periodic draining of the trap. Mass spectral analysis of the reaction mixture at this time indicated that no starting material was present. To the cooled solution sodium acetate (0.3 g) was added, the hexane layer was decanted, diluted with a small amount of ether and washed three times with a 2% sodium acetate solution. The ethylene glycol layer, diluted with H O, was extracted with ether, and this ether phase after washing with 2% sodium acetate solution was combined with the ether-hexane layer and evaporated in vacuo. The white residue, recrystallized from ethyl acetate gave 12.6 g (76%) of 6,6-ethylenedioxy-5acholestan-3Bol (3). m.p. l14l 15; mass spectrum: m/e 446 (M*, 26%, C H O requires 446, 291 100% 183 25% nmr (CDCI3) 6 3.90 (m, ketal); ir (KBr) 3350 cm" (OH); Anal. calcd, for C H O C, 77.97; H, 11.28; found: C, 77.79; H, 11.49.

A solution of 6-ethylenedioxy-5oz-cholestan-3/3-(3, 12.5 g) in pyridine was added to iceco1d pyridine-CrO- complex prepared by adding CrO 182 g) to ice-cold pyridine (182 ml). An additional amount of pyridine ml) was utilized for complete transfer. The mixture was allowed to come to room temperature and stirred for 10 hr. It was then brought to a volume of 500 ml with ethyl acetate and filtered through a column packed with Celite (a diatomaceous silica product marketed by Johns-Manville Co.) (50 g, 4 cm diameter) slurried in ethyl acetate. Material eluted with a total of 750 ml of ethyl acetate was collected, and filtered through a 6 cm column packed with alumina g) slurried in ethyl acetate. After elution with 1200 ml of ethyl acetate and evaporation of the solvent, a greenish solid was recovered. This was applied to a 2 X 23.5 cm (50 g alumina, A6 7 minus 200 mesh) column and eluted with ethyl acetate. The first ml of eluant gave 12.3 g (98%) of pure 6,6-ethylenedioxy-5acholestan-ll-one (4). An analytical sample recrystallized from MeOH was obtained as white crystals: m.p. 115116; nmr (CDC1 8 2.35 (m. C-2 and C-4 protons). 3.9 (m. ketal); ir (KBr) 1710 cm (C=O)', mass spectrum: m/e 444 (M*. 19%, C H O C. 78.33; H, 10.88; obs: C, 78.37; H. 10.93.

To a solution of 10.9 g of ketone 4 in 218 ml THF cooled to 9, a solution of 1.21 g KOAe and 1.31 ml Br; in 12.3 ml acetic acid was added dropwise with stirring, allowing the solution to decolorizc between additions. The solution was then poured into 200 ml of cold 2% NaOAc solution, and the product extracted into ether. The product. according to tlc. consisted of ca. 50% bromo compound and 50% starting material. After evaporation of the solvent, the residue was taken up into methano1/CH C1 l :1 from which upon standing 3.91 g of the 2-bromo compound (5) separated: mass spectrum. m/e 524, 522 (M*), 443 (M Br). 291; nmr (CDCl:,) 8 4.8 (dd, .l=6, 14 Hz, C-2-H), 3.9 (ketal).

Crude 5 (3.91 g) was added to 3.1 g CaCO in 39 ml boiling DMA. Reflux was continued for 15 min, the mixture diluted with ether and thoroughly extracted with H O. Evaporation of the ether gave a pale yellow solid which was applied to an activated silicic acid column (150 g). Elution with 20% ethyl acetate in Skellysolve B (5 ml fractions) gave in fraction 42-54, A compound.6,6-ethylenedioxy-5a-cholestl -ene-3-one (6). as an amorphous solid (2.7 g. 25% from 4) but homogeneous on tlc (R; 0.62). 1:3 ethyl acetate/Cyclohexane): uv (95% EtOl-Uk 227 nm (E8340); ir (CHCl 2920, 1675 cm, nmr (CDCl- 87.12 (1H. d, .1=lHz), 5.85 (IH, d, J-10Hz), 3.9 (4H, m, ketal); mass spectrum, m/c (rel. int.) 442 (M", 36%), 291 (100%); high resolution mass spectral Anal. calcd. for C H O 442.3447; found: 442.3452.

To 2.09 g A'-steroid (6) in 25 ml dioxane, 6 ml of 1N NaOH and 4.25 ml of 30% H 0 were added. After standing for 20 hr at room temperature, water was added, and the solution was extracted several times with benzene and ether. The residue remaining after evaporation of the combined organic phases was applied to a silicic acid solumn (30 g) and eluted (as l 1 ml fractions) first with 10% ethyl acetate in Skellysolve B, then with 20% ethyl acetate in Skellysolve B, giving 1.4 g (65%) of the epoxide, 6,6-ethylenedioxy-la,2aepoxy-a-dholestan-3-one (7). Crystallization from Skellysolve A and then from methanol gave material of m.p. 98.5-100; nmr (CDCI 839 (m, 4H), 3.46 (d, 1H, J=4.2 Hz), 3.2 (d. 1H, J=4.2Hz); high resolution mass spectrum, m/e (rel. int.) 458.3396 (227', Mi calcd. for C ,,H O 458.3396). 29] (100%); Anal. calcd, for C ,,H O C, 75.94; H, 1011; found: C, 75.71; H. l().27.

A solution of 2.0 g of epoxide 7 in 15 ml of hydrazine hydrate was refluxed for 15 min, then diluted with 50 ml H 0, and extracted three times with ether. The ether layer was washed with 20 ml H O, dried over N21 S0 and evaporated. The residue was applied to a silicic acid column 180 g) in Skellysolve B. Elution with mixtures of ethyl acetate/Skellysolve 8(200 ml of 2% ethyl acetate in Skellysolve B, followed by 200 ml of 5%, 300 ml of 200 ml of 600 ml of and finally 200 ml of ethyl acetate in Skellysolve B) gave (in the 20% ethyl acetate solvent) 720 mg of the oily la-hydroxy compound, 6,6-ethylenedioxy-lahydroxy-Soz-cholest-Z-ene (8). which was homogeneous on tlc. After several weeks at 4C, this oily compound solidified, m.p. 8490C; nmr (CDCl 83.66 (1H. m, C-l 3.93 (4H, m. ketal), 5.85 (2H, m. C-2,3 mass spectrum. m/e (rel. int.): 444 (66, M), 375 291 A solution of 720 mg of the la-hydroxy compound 8 in 60 ml cyclohexane was hydrogenated under 1 atm H at room temperature for 4 hours, using 700 mg 5% Pd/C as catalyst. The solution was then filtered, the filtrate evaporated to dryness and the residue recrystallized from Skellysolve B to give 660 mg (92% yield) of 6,6-ethylenedioxy- 1 a-hydroxy-Sa-cholestane (9 m.p. 96-98C; nmr (CDCl 83.65 (m. 1H, C-l 3.93 (4H. m. ketal); ir (CHCl 3480 cm" (OH), 1205-1400 cm (4 bands, ketal) mass spectrum m/e (rel. int.): 446 (39, M), 291 100). Anal. calcd. for (3 ,14, 0 C. 77.94; H, 11.28; found: C, 78.07; H, 11.54.

Ketal 9 (660 mg) was dissolved in 8 ml of MeOH and 10 ml 95% EtOH containing 40 mg p-toluene sulfonic acid monohydrate was added. This solution was stirred at room temperature for 16 hours. Then a 5% NaHCO solution was added and after extraction with ether, drying (Na SO and evaporation of the solvent. the residue was recrystallized from methanol/ether to give colorless crystals of m.p. l8l-l83 (quantitative yield). nmr (CDCl 83.75 (m. 1H, C-l ir (Cl-1C1 3480 (OH). 1700 cm (C=O); mass spectrum, m/e (rel. int.): 402 (83, M), 384 (86), 369 (20), 367 (23), 331 (49), 289 (43), 271 (23), 247 (23), 229 (60) identifying 1a-hydroxy-5a-cholestan-6-one (10).

The la-aleohol 10 was acetylated in 12 ml of Ac O and 2 ml of pyridine at 50C for 36 hours. After addition of 25 ml of H 0 the product was extracted into ether. Drying (Na SO and evaporation of the ether gave after recrystallization of the residue from hot methanol, 400 mg white crystals la-acetoxy-Sacholestan-6-one l 1 m.p. 104-l05; nmr (CDC1 82.13 (s, 3H, C-1-OAc), 4.98 (m, 1H,C-l ir (CHCl 1710. 1730 cm (ketone and acetate); mass spectrum, m/e rel. int.): 444 (49, M*), 384 (84), 366 (48), 229 (26). Anal. calcd. for C H O C, 78.33; H, 10.88; found: C, 77.56; H, 11.04.

To a solution of 300 mg of compound 1 l in 20 ml of isopropanol, 64 mg of NaBH. (2.5 x mole) dissolved in 5 m1 of isopropanol was added. After stirring at room temperature for 16 hours, 20 ml of H 0 containing 1 drop of 3% H 80 was added. Extraction with ether (3 X) drying (Na SO.) and evaporation of the combined other layers, gave a residue which was chromatographed on silicic acid 15 g). Elution with 20% ethyl acetate in Skellysolve B yielded 260 mg of the pure 6B- alcohol-la-acetoxy-Sa-cholestanbfi'ol l2). Crystallization from MeOH gave white needles. mp. l27-l28C-, nmr (CDCh) 52.06 (s, 3H. C-l-OAe), 3.86 (m. 1H, C6), 4.75 (m, 1H, C-l); ir (CHCl 3480, 1725 cm (OH. acetate); mass spectrum m/e (rel. int.): 446 (1.2, M), 428 13), 386 (39), 368 (100), 255 (25), 231 (23), 228 (52), 213 (45).

To an icecold pyridine solution (0.5 m1) of 255 mg of the alcohol 12. 0.8 ml of POCI was added dropwisc. The solution was then kept at room temperature for 5% hours. After addition of ice-water. the solution was ex tracted with ether (3 X). The combined ether fractions were dried over Na SO and evaporated. The residue was applied to a 10 g silicic acid column in Skellysolve B. Elution with 60 ml Skellysolve B and then 10% ethyl acetate in Skellysolve B gave in fractions -12 (8-m1 fractions) the compound la-acetoxy-cholest5-enc (13) (yield 230 mg). Crystallization from ethanol pro duced white crystals of m.p. 66C; nmr.(CDCl;,) 82.05 (s, 3H, C-l-OAc), 4.98 (m, 1H, C-1-),5.45 (m, 1H, C-6); ir (CHCI 1725 cm (acetate); mass spectrum m/e (rel. int.): 368 (100, M*-60.), 255(39), 247 (34), 219 (24), 213 (28). Anal. calcd. for C ,,H O C, 81.25; H, 11.29; found: C, 81.42; H, 11.38.

The l-acetoxy compound 13 (150 mg) dissolved in 2 ml of Skellysolve B and 2 m1 of benzene, was treated with N,N'-dibromo-5,5-dimethyl hydantoin. The solution was kept at for 10 min., then cooled in an ice bath for 5 min., and filtered. The filtrate was taken up in 2 m1 of xylene and added dropwise to a preheated solution of 0.25 ml trimethyl phosphite in.1 m1 xylene at 135. After 1.75 lhours at 135, the solvent was evapo-.

trum (ethanol) A 295, 283, 273 nm; mass spectrum,

derivative 1a-acetoxy-5,6-cholestadiene (14). Ultraviolet spec- 5 products were separated on a column of AgNO impregnated silicic acid (5 g) prepared as a slurry in Skellysolve B. Elution with 5% ether in Skellysolve B gave two main fractions. The nonpolar fraction (tube No. 8-1 1; 3.2m1 fractions), exhibiting uv absorption at 10 A 260 nm and A 235 mm, contained the desired previtamin D derivative. Warming for 3 hours in ethanol under N produced an enhancement of the optical density indicating isomerization of the pre-vitamin to the vitamin skeleton. The mixture was then saponified 15 with two drops of 0.9 N KOH in methanol at 60 for 10 min. Addition of water, extraction with CHCl drying of the CHCl phases and evaporation, gave after chromatography of the residue on LH-20 (20 g) and elution with CHCl zskellysolve B (1:1), the desired product,

20 3-deoxy-1a-hydroxycholecalciferol (15'). uv (ethanol) A 264.5 pm )t,,,,-,, 229 mu; mass spectrum, m/e (rel. int.): 384 (19, M), 366 (8), 271 (7), 253 (7), 136

SCHEME 1 -Continued gas and stirred at room temperature for 15 hours. Addition of 50 ml of 4% aqueous KHCO and 50 ml of ether followed by further extraction with ether, washing of the ether extracts with 2% HCl, drying (Na,SO and 5 finally evaporation of solvent gave la acetoxycholesterol tosylate (l8); nmr (CDCl 87.82, 7.38 (4H, aromatic H). 5.50 (1H, m, 06), 4.90 (m, m, C-l); 3.75 (1H, m, C-3 2.49 (3H, s, tosylate methyl), 1.98 (3H, s, OAc). l0 A solution of 0.900 mg of the tosylate 18 in 50 ml of benzene was stirred and purged with N Upon addition on of 2.3 ml of Vitride reagent (a solution of 70% Na bis(2-methoxyethoxy aluminum hydride in benzene, Aldrich Chemical Co. the mixture was refluxed (80) 15 for 18 hours. The product was isolated in the usual An alternative method for preparing 3-deoxy-l manner: after addition of water and 1.0 ml of 10% hydroxycholecalciferol is set forth in the following de- NaOH, the inorganic precipitate was removed by filtrascription and in the following process schematic where tion and washed with ether, the aqueous phase was furlike numbers identify like compounds. ther extracted with ether, and the combined organic A solution of 600 mg of la-hydroxycholesterol diac- 20 extracts were washed (10% NaOH), and dried over etate (l6) in 1.6 ml of diethyl ether was cooled to ice- Na,SO and evaporated in vacuo. Chromatography of bath temperature and 1.6 ml of0.lN KOH in methanol this residue on silica gel (using 20% ethylacetate in was added slowly with stirring. After stirring for 2.5 Skellysolve B) gave pure la-hydroxycholest-S-ene hours, acetic acid (0.25 ml) and water was added, the (19). nmr (CDCl 85.53 (1H, m, C-6), 3.74 (1H, m, mixture was extracted with ether (3 X), combined ex- C-l mass spectrum, m/e 386 (M*), 371, 368, 273. tracts were dried (Na,SO.,) and evaporated to dryness A solution of 140 mg of compound [9 in 6 ml of dry to give 0.55 g of la-acetoxycholesterol 17), homogepyridine was treated with 6 ml of acetic anhydride and neous on tlc. nmr (CDCl 85.55 (1H, broad, C-6), refluxed overnight. The solution was evaporated to dry- 5.00 (1H, m, C-l), 3.62 (1H, m, C-3), 2.10 (3H, s, ness and the residue was chromatographed on a silica OAc). gel column using Skellysolve B as the solvent. Pure 1a- The la-acetoxycholesterol 17) was dried by dissoluacetoxycholest-5-ene (l3) was recovered. tion in benzene, evaporation of solvent and further dry- Conversion of the la-acetoxycholest-S-ene to 3- ing under vacuum. The amophous material (0.55 g) deoxy-la-cholecalciferol, i.e. conversion of compound was then taken up in pyridine, 0.6 g of toluene sulfonyl l3 to compound 14 to compound l5 was carried out as chloride was added, the mixture purged with nitrogen described above.

SCHEME II Ill Biological Activity Male weanling rats were housed in hanging wire cages and fed ad libritum the low calcium vitamin D- deficient diet described by Suda et al (J. Nutr. 100, 1049 (1970)) for 3 1/2 weeks prior to their use in the following assays.

Intestinal Calcium Transport The rats were divided into groups of 6 with the test rats receiving 0.25 ug of 3-deoxyl ahydroxycholecalciferol dissolved in the anal intrajugularly and the control animals receiving 0.05 ml of 95% ethanol. After 12.5 hours all rats were decapitated and the blood and duodena were collected. The duodena were prepared according to the techniques of Martin and DeLuca (Am. J. Physiology 2l6, 1351 (1969)). Aliquots from serosal and mucosal media were spotted on filter paper discs, dried and placed in 20 ml counting vials containing 10 ml of scintillation solution. Results are shown in the table below.

Table 1 Material Ca serosal/Ca Mucosal Control (ethanol) 1 9 J2" 3-deoxy-la-hydroxycholccal- 3.4 x 0.4

ciferol Average of 6 rats Calcium Mobilization from Bone The blood obtained from the rats (see below) was centrifuged and 0.l ml of the serum obtained was mixed with 1.9 ml of 0. l% NaCl solution. Serum calcium concentration was determined with an atomic absorption spectrophotometer (Perkin-Elmer Model No. 214). Results are shown in Table 2 below.

Table 2 Material Serum Ca*( mg Control (ethanol) 4.5 i 0.2 3-deoxyl a-hydroxycholecalciferol 8 i 0.2

Average of 6 rats 3-deoxyl aconverting cholesterol into its 6-keto form, 3p-

hydroxy-Sa-cholestan-G-one;

converting the said keto form into its corresponding ketal, 6,6-ethylenedioxy-5 a-cholestan-3B-ol;

oxidizing the said ketal and recovering 6,6-

ethylenedioxy-Sa-cholestan-3-one;

subjecting the said S-ketone to bromination and dehydrobromination in sequence and recovering the A compound, 6,6-ethylenedioxy-5a-cholestl -en- 3-one;

expoxidizing the said A compound and recovering 6,6-

ethylenedioxyl a,2a-epoxy-5 ct-cholestan-3-one;

treating the recovered epoxy compound with hydrazine and recovering the unsaturated alcohol 6,6- ethylenedioxyla-hydroxy-S a-cholest-2-ene;

catalytically reducing the recovered unsaturated alcohol to obtain the ketal 6,6-ethylenedioxy-lahydroxy-Sa-cholestane;

converting the said ketal to the corresponding ketone and acetylating the ketone to obtain la-acetoxy-Sachoiestan-6-one;

treating the acetylated compound with a hydride reducing agent and recovering the alcohol, la-acetoxy- 5a-cholestan-6fiol;

dehydrating the recovered alcohol and recovering l a-acetoxycholest-S-ene;

subjecting the recovered la-acetoxycholest-S-ene to allylic bromination and dehydrobromination with trimethyl phosphite and recovering la-acetoxy-5,7- cholestadiene;

irradiating the said diene with ultraviolet radiation and recovering 3-deoxyl a-acetoxy precholecalciferol;

thermally promoting isomerization to 3-deoxy-laacetoxy-cholecalciferol, hydrolyzing the said compound and recovering 3-deoxyl ahydroxycholecalciferol. 3. A method for preparing 3-deoxyl crhydroxycholecalciferol.

l t t 

1. 3-DEOXY-1$-HYDROXYCHOLECALCIFEROL.
 2. A method for preparing 3-deoxy-1 Alpha -hydroxycholecalciferol which comprises: converting cholesterol into its 6-keto form, 3 Beta -hydroxy-5 Alpha -cholestan-6-one; converting the said keto form into its corresponding ketal, 6,6-ethylenedioxy-5 Alpha -cholestan-3 Beta -ol; oxidizing the said ketal and recovering 6,6-ethylenedioxy-5 Alpha -cholestan-3-one; subjecting the said 3-ketone to bromination and dehydrobromination in sequence and recovering the Delta 1 compound, 6,6-ethylenedioxy-5 Alpha -cholest-1-en-3-one; expoxidizing the said Delta 1 compound and recovering 6,6-ethylenedioxy-1 Alpha ,2 Alpha -epoxy-5 Alpha -cholestan-3-one; treating the recovered epoxy compound with hydrazine and recovering the unsaturated alcohol 6,6-ethylenedioxy-1 Alpha -hydroxy-5 Alpha -cholest-2-ene; catalytically reducing the recovered unsaturated alcohol to obtain the ketal 6,6-ethylenedioxy-1 Alpha -hydroxy-5 Alpha -cholestane; converting the said ketal to the corresponding ketone and acetylating the ketone to obtain 1 Alpha -acetoxy-5 Alpha -cholestan-6-one; treating the acetylated compound with a hydride reducing agent and recovering the alcohol, 1 Alpha -acetoxy-5 Alpha -cholestan-6 Beta -ol; dehydrating the recovered alcohol and recovering 1 Alpha -acetoxycholest-5-ene; subjecting the recovered 1 Alpha -acetoxycholest-5-ene to allylic bromination and dehydrobromination with trimethyl phosphite and recovering 1 Alpha -acetoxy-5,7-cholestadiene; irradiating the said diene with ultraviolet radiation and recovering 3-deoxy-1 Alpha -acetoxy precholecalciferol; thermally promoting isomerization to 3-deoxy-1 Alpha -acetoxy-cholecalciferol, hydrolyzing the said compound and recovering 3-deoxy-1 Alpha -hydroxycholecalciferol.
 3. A method for preparing 3-deoxy-1 Alpha -hydroxycholecalciferol which comprises: hydrolyzing 1 Alpha -hydroxycholesterol diacetate and recovering 1 Alpha -acetoxycholesterol; tosylating the recovered compound and extracting 1 Alpha -acetoxycholesterol-tosylate from the reaction mixture; reducing the tosylate with a hydride reducing agent and isolating 1 Alpha -hydroxycholest-5-ene from the reduction reaction mixture; acetylating the isolated compound and recovering 1 Alpha -acetoxy-cholest-5-ene; subjecting the recovered 1 Alpha -acetoxycholest-5-ene to allylic bromination and dehydrobromination with trimethyl phosphite and recovering 1 Alpha -acetoxy-5,7-cholestadiene; irradiating the said diene with ultraviolet radiation and recovering 3-deoxy-1 Alpha -acetoxy-precholecalciferol; thermally promoting isomerization to 3-deoxy-1 Alpha -acetoxy-cholecalciferol, hydrolyzing the said compound and recovering 3-deoxy-1 Alpha -hydroxycholecalciferol. 